NM_000441.2(SLC26A4):c.1667A>G (p.Tyr556Cys) AND Autosomal recessive nonsyndromic hearing loss 4

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Aug 1, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000515668.6

Allele description [Variation Report for NM_000441.2(SLC26A4):c.1667A>G (p.Tyr556Cys)]

NM_000441.2(SLC26A4):c.1667A>G (p.Tyr556Cys)

Gene:

SLC26A4:solute carrier family 26 member 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q22.3

Genomic location:

Preferred name:

NM_000441.2(SLC26A4):c.1667A>G (p.Tyr556Cys)

HGVS:

NC_000007.14:g.107700135A>G
NG_008489.1:g.44501A>G
NM_000441.2:c.1667A>GMANE SELECT
NP_000432.1:p.Tyr556Cys
NC_000007.13:g.107340580A>G
NM_000441.1:c.1667A>G
p.Tyr556Cys

Protein change:

Y556C

Links:

dbSNP: rs763006761

NCBI 1000 Genomes Browser:

rs763006761

Molecular consequence:

NM_000441.2:c.1667A>G - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

loss_of_function_variant [Sequence Ontology: SO:0002054]

Observations:

Condition(s)

Name:: Autosomal recessive nonsyndromic hearing loss 4 (DFNB4)
Synonyms:: NEUROSENSORY NONSYNDROMIC RECESSIVE DEAFNESS 4; DEAFNESS, AUTOSOMAL RECESSIVE 4, WITH ENLARGED VESTIBULAR AQUEDUCT, DIGENIC; Nonsyndromic enlarged vestibular aqueduct (NSEVA); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010933; MedGen: C3538946; Orphanet: 90636; OMIM: 600791

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000611819	Division of Hearing and Balance Research, National Hospital Organization Tokyo Medical Center	criteria provided, single submitter (Submitter's publication)	Pathogenic (Jul 1, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000994899	National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center See additional submitters The Hugh Knowles Center for Clinical and Basic Science in Hearing and Its Disorders, Northwestern University	no assertion criteria provided	Affects (Aug 20, 2019)	germline	clinical testing, in vitro	PubMed (3) [See all records that cite these PMIDs] 9618167, 11932316, 31599023
SCV002026955	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 5, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004201900	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Aug 1, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing, in vitro
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Subgroups of enlarged vestibular aqueduct in relation to SLC26A4 mutations and hearing loss.

Okamoto Y, Mutai H, Nakano A, Arimoto Y, Sugiuchi T, Masuda S, Morimoto N, Sakamoto H, Ogahara N, Takagi A, Taiji H, Kaga K, Ogawa K, Matsunaga T.

Laryngoscope. 2014 Apr;124(4):E134-40. doi: 10.1002/lary.24368. Epub 2013 Dec 17.

PubMed [citation]

PMID:: 24105851

Molecular analysis of the PDS gene in Pendred syndrome.

Coyle B, Reardon W, Herbrick JA, Tsui LC, Gausden E, Lee J, Coffey R, Grueters A, Grossman4 A, Phelps PD, Luxon L, Kendall-Taylor P, Scherer SW, Trembath RC.

Hum Mol Genet. 1998 Jul;7(7):1105-12.

PubMed [citation]

PMID:: 9618167

See all PubMed Citations (5)

Details of each submission

From Division of Hearing and Balance Research, National Hospital Organization Tokyo Medical Center, SCV000611819.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, SCV000994899.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)
2	not provided	not provided	not provided	not provided	in vitro	PubMed (3)

Description

in vitro experiment

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided
2	germline	yes	not provided	not provided	assert pathogenicity		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV002026955.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004201900.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 6, 2024

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